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Title: A quantitative analysis of hemodynamic forces on cellular response
Author: White, Alex
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2013
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Mechanical forces are known to be important in various physiological and pathological processes, including the development of atherosclerosis. In particular it is believed that abnormal shear stress, transduced by the vascular endothelium, is particularly important in promoting atherogenesis. However, it is still unclear to what extent the precise details of the mechanical environment to which the vascular endothelium is subjected affect its response. Therefore, a novel flow-bioreactor system has been developed which is capable of subjecting endothelial cells cultured in vitro to various mechanical parameters at similar levels to those applied in vivo. The fluid dynamics within the flow-bioreactor system has been analysed computationally to accurately quantify the mechanical forces experienced by cells cultured within the flow-bioreactor system, and a validation of the computational model used has been performed to ensure the accuracy of the results of the computational fluid dynamics analysis. The flow bioreactor system has been used to subject human endothelial cells to physiologically realistic mechanical forces for up to 24 hours. The cells were shown to realign in the direction of the shear stress and elongate in response to the application of WSS, consistent with the results shown both in other mechanical models and in vivo. A computational image processing programme has been developed to accurately quantify the morphology of cells. Quantitative analysis using this programme showed that the degree of realignment and elongation was significantly dependent on the local cell density. The enabling technologies developed during this project may help with future work aimed at elucidating the features of the mechanical environment which are important in promoting or suppressing atherogenesis.
Supervisor: Chong, Chuh K. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available